The immune system has evolved to protect animals from pathogens. The cells which mediate immunity include lymphocytes and phagocytes. Lymphocytes recognize antigens on pathogens, and phagocytes internalize pathogens and degrade them. An immune response consists of two phases: In the first phase, an antigen activates specific lymphocytes whose receptors recognize it; in the second phase, the effector phase, the activated lymphocytes coordinate an immune response that eliminates the source of the antigens. Lymphocytes consist of different cells with specialized functions. B cells make antibodies, which recognize and bind to antigens; cytotoxic T cells kill virally infected cells; Helper T cells coordinate the immune response by direct cell-cell interactions and the release of cytokines, which help B cells make antibody; and macrophages kill parasites that have invaded them. B cells usually recognize intact antigen molecules, while T lymphocytes recognize antigen fragments on the surface of other cells.
All lymphocytes are derived from bone-marrow stem cells, but T cells develop in the thymus, while B cells develop in the bone marrow. B cells differentiate from lymphoid cells into virgin B cells, and then may be driven by antigen to become memory cells or plasma cells. The genes coding for antibody are rearranged during the course of B cell development. B-cell maturation and differentiation is an ordered and complex process that ultimately results in the expression of antibodies (i.e., immunoglobulins, or Igs). Antibodies are extremely important components of the immune system, due to their recognition of and binding to antigens, as well as to their involvement in the initiation of various biologic processes that are independent of antibody specificity
However, the immune system may break down; this can lead to immunodeficiency or hypersensitivity diseases, or to autoimmune diseases. Immunodeficiency results when any elements of the immune system are defective, resulting in an inability to fight infections adequately. Some immunodeficiencies are genetic, while others, such as AIDS, are acquired. Hypersensitivity results from immune reactions which are disproportionate to the damage that could be caused by a pathogen, or where the immune system mounts a reaction to a harmless antigen, such as a food molecule. In a hypersensitivity response, the immune reaction may cause more damage than the pathogen or antigen. Examples of hypersensitivity include hay fever and asthma. Autoimmunity results from an inappropriate reaction to self antigens. The immune system normally recognizes all foreign antigens and reacts against them, while recognizing the body's own tissues as “self;” however, in autoimmunity, the system reacts against self components. Examples of autoimmune diseases include rheumatoid arthritis and pernicious anaemia.
One source of immune system breakdown is the complexity of the development and interactions of the different components if the immune system. As the pathway of B-cell development is complicated and involves numerous factors and interactions, there are many opportunities for errors and/or abnormal development. As noted above, one such set of errors is the loss of tolerance of “self,” with the resultant production of autoimmune disease. In addition, various leukemias (e.g., chronic lymphocytic leukemia) and other malignant conditions may arise during abnormal B-cell development. Thus, there is a need to prevent abnormal B-cell development and/or activation. To date, current methods to prevent abnormal B-cell development and/or activation appear to adversely impact innate and/or T-cell mediated (i.e., cell-mediated) immunity. Thus, there is also a need to prevent abnormal B-cell development without interfering with innate or T-cell mediated immune function.